Chemical conditionality: A genetic strategy to probe organelle assembly
Chemical conditionality: A genetic strategy to probe organelle assembly
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DOI：
10.1016/j.cell.2005.02.014
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发表时间：
2005-04-22
期刊：
影响因子：
64.5
通讯作者：
Silhavy, TJ
中科院分区：
文献类型：
--
作者：
Ruiz, N;Falcone, B;Silhavy, TJ
大肠杆菌外膜（OM）的组装知之甚少。虽然洞察基本的细胞过程往往是从研究突变体，OM缺陷型突变体没有很大的信息，因为他们通常有非特异性的渗透性缺陷。在这里，我们表明，有毒的小分子可以用于选择采用具有渗透性缺陷的菌株，以创造特定的化学条件，需要特定的抑制突变。抑制子表型与小分子的物理性质相关，但突变不在其靶基因中。相反，突变通过部分恢复细胞膜的不透性而使细胞存活。使用“化学条件性”，我们鉴定了yfgL中的突变，并且，在这里和Wu等人发表在本期Cell上的随附论文中（Wu等人，2005），我们表明YfgL是参与OM（3桶蛋白）组装的多蛋白复合物的一部分。我们认为，小组的有毒小分子将是有用的，以产生化学条件，使识别所需的基因在其他生物体中的细胞器组装。
The assembly of the Escherichia coli outer membrane (OM) is poorly understood. Although insight into fundamental cellular processes is often obtained from studying mutants, OM-defective mutants have not been very informative because they generally have nonspecific permeability defects. Here we show that toxic small molecules can be used in selections employing strains with permeability defects to create particular chemical conditions that demand specific suppressor mutations. Suppressor phenotypes are correlated with the physical properties of the small molecules, but the mutations are not in their target genes. Instead, mutations allow survival by partially restoring membrane impermeability. Using "chemical conditionality," we identified mutations in yfgL, and, here and in the accompanying paper by Wu et al. published in this issue of Cell (Wu et al., 2005), we show that YfgL is part of a multiprotein complex involved in the assembly of OM (3 barrel proteins. We posit that panels of toxic small molecules will be useful for generating chemical conditionalities that enable identification of genes required for organelle assembly in other organisms.